What if cancer is an organism?
Messy thoughts on the atavistic theory of cancer and biohacking
Hi, I’m Melyne! You may notice today’s post is a little different. I will still use this newsletter to share occasional updates, but more often to write out interesting thoughts from my rabbit holes. I hope you enjoy this one!
Our story begins with the largest carnivorous marsupial: the Tasmanian devil, a scavenger the size of a small dog. Famous for their aggressive, loud screams, devils are often biting into each other during mating or feeding. Unfortunately, this very habit is part of what drives them towards extinction.
When a devil is bitten, Schwann cells surrounding wounded nerves quickly switch into a repair mode at the site of injury to heal the damage. At some point in history, this repair mode never turned off. These Schwann cells proliferated out of control and eventually became cancer cells. This is the birth of Tasmanian devil facial tumor disease (DFTD).
What makes DFTD so interesting isn’t how it started, but how it spreads. Unlike most cancers which die with their host, DFTD survives by passing directly from one devil to another through biting.
Which begs the question: where do we classify DFTD in the taxonomy of life?
A mind of its own
There is a case to be made that DFTD is an organism in its own right. I think it’s easier to accept this paradigm, given DFTD travels externally from body to body. But what if we see the cancers in our bodies through this same lens?
Let’s backtrack. We like to think of cancer as being selfish, but perhaps cancer cells are no more selfish than normal cells. Normal somatic cells sacrifice their individual survival in favor of the organism as a whole. They limit their growth to maintain overall tissue architecture (controlled proliferation); they sacrifice themselves for the greater good (apoptosis).
Conversely, in early stages, cancer cells start to break away from the larger collective of tissues. They forget they are part of the rest of the body, so instead of pursuing larger scale goals, they pursue goals of their own.
The case of atavism
In recent years, transcriptomic analysis has revealed cancer cells often overexpress various phylogenetically ancient genes which are hallmark in unicellular organisms. The atavistic hypothesis posits cancer behaves like and regains the goals of our unicellular ancestors, who pursued the ultimate goal of ensuring survival within the surrounding environment before multicellularity evolved.
It is proposed that facing an environmental threat to the health of a cell triggers this ancient instinct to kick in, which makes sense from a behavioral perspective. Cancer cells proliferate in a state of biological immortality with unregulated self-replication, the same way bacterial biofilms evolved to form to ensure survival. Metastasis is colonization of the environment, cancer’s way to explore and exploit fresh resources while dispersing risk in the case of biofilm destruction.
From unicellular to proto-multicellular
Our unicellular ancestors billions of years ago lived in shallow seas and rocks, in a time before soil existed. They were adapting to threats like heat, UV radiation, and fluctuations in pH of their environment. But here’s what is remarkable to me. Despite starting out with atavistic goals, it must learn to preserve these goals while navigating the much smarter environment that is the human body.
At first, this sucks for cancer. The rest of the body is highly coordinated, and is trained detect and destroy at the first sign of cancer. Which is why cancer needs a better strategy. It starts off by working in stealth, learning to evade detection from the diligent guards in the immune network by downregulating tumor antigens. This way, it can begin to remodel its environment to optimize for proliferation, slowly growing a tumor.
Once the tumor has grown so large that the immune system notices, cancer finds the switch to deactivate some soldiers (i.e. binding PD-L1 on T-cells). It even recruits an army of immunosuppressive cells (i.e. Tregs and TAMs) to regulate and protect against immune attacks—this makes me think of that zombie-ant fungus.
Then, cancer decides to strike. It hitches a ride through vascular networks to repeat this process, and furthering the goals of the colony. It adapts accordingly to do this (i.e. EMT, which is a matter of changing both morphology and function). Cancer adaptivity still amazes me, especially in the case of complex behaviors like vasculogenic mimicry and cannibalism/entosis, though these are topics for another time.
This is my take given a blatant personification of cancer as the protagonist of our story. But story aside, I believe cancer starts out, at early stage, following unicellular goals via proliferation. Somewhere along the line, it becomes something like a proto-multicellular organism.
Some final thoughts
So why does all this matter? Colorful storytelling aside, understanding cancer through this lens may help to contextualize our biggest problems in cancer research. We can even extend it: what if we see all diseases as organisms? What changes about how we understand and treat them?
The traditional paradigm targets specific molecular drivers, blocking certain pathways promoting proliferation. But cancer is smart, adapting to develop drug resistance, and it becomes a race of how quickly drug development can catch up (by the looks of it, we’re losing this one). I believe we need to develop solutions that work at a higher level, rather than micromanaging biology.
This concept of biohacking is fascinating to me. I define biohacking as the process through which one agent exploits the capabilities of another agent to achieve its own goals (let’s talk if you see differently!). In particular, the early detection problem in cancer becomes a problem of spotting this biohacking, goal misalignment, and subsequent transition to a proto-multicellular state. For cancer, it’s hard to win against smart agents, but even better if you can trick them into working for you.
I still have many questions. Where do we draw the line between disease and the host it inhibits? What kinds of experiments can we design to characterize the problem-solving capabilities of cancer in the way we would a new organism? What would it look like to simulate a “body vs. cancer” system, one as a larger multicellular body with the goal of maintaining the status quo, and another with the goal of proliferating as much as possible? Is it possible for a cellular agent of any kind (i.e. biobots) to pursue goals as aggressively and effectively as cancer does, while still valuing the goals of the collective above its own survival? Is stress the universal trigger? And how can we test all this?
There’s that thought experiment for incoming PhDs, that goes: “If you met a magical genie who would give you the answer to just a single scientific question, what would you ask?” I’m going to need lots of genies.
Views are my own. The purpose of this post is to explore interesting ideas which I find compelling, not to assert definitive truths. I am inspired by the work of Paul Davies and Michael Levin. Much thanks to Michael Levin for many conversations, and for developing a rich set of theories and studies from which I could pull upon to expand my own thinking.
Thanks for reading! As always, feel free to reach out on LinkedIn or on X if you’d like to discuss anything I’ve written here.